This proposal is a next step in identifying relevant outcome measures for clinical trials. Considerable data on the late onset Tay-Sachs (LOTS) and Sandhoff (LOSD) patients has recently been collected at two sites (Massachusetts General Hospital and the NIH Clinical Center) as well as the last two NTSAD Annual Family Conferences and this exploratory study would expand the range of outcomes to metrics relevant to the daily lives of LOTS and LOSD adults, including their ability to move about and participate in the activities of daily living.

This is a 6 month exploratory study using 5-8 ambulatory or partially ambulatory adult patients with late onset Tay-Sachs or Sandhoff disease to collect patient data on ambulation, falls, and wake/sleep cycles and other patient input that can be tested as clinically relevant outcome measures for future clinical trials. Data is collected through a wearable device and transmitted through a mobile app to Dr. Tifft for analysis. The data collected will be compared to clinical testing including gait lab metrics to be conducted at the NIH Clinical Center at the time of initial evaluation and at the 6 month endpoint.

June 2015

NTSAD Research Initiative Grants supported by the Katie & Allie Buryk Research Fund

This project aims to develop a both a clinical registry and a repository of samples for Late Onset GM2 Gangliosidoses. The registry will use the NeuroBANK platform to create and implement use of electronic case report forms, allowing standardized data to be collected from patients with LOTS. Review of current medical literature and surveys of patients will help determine which data to include in the registry in order to establish meaningful outcome measures. Prospective evaluations of patients will also be used to determine these optimal outcome measures, looking at change over time, patient value of measures, and variability among patients. Samples collected will be used to identify potential biomarkers of disease progression and to correlate these biomarkers with clinical outcomes. Both clinical outcome measures and biomarkers are essential components of clinical trial readiness, necessary to show effect of any experimental therapy.

This project supports the development of a mouse model for Late Onset Tay Sachs and Sandhoff diseases. Mice with Sandhoff disease are used to study both diseases because both store GM2 gangliosides and because mice with mutations in the HEXA gene which causes TSD do not develop features of TSD due to an alternate pathway for GM2 degradation. This model is different from currently existing SD mouse models in that it has a specific mutation that leads to residual enzyme, as is seen in the late onset forms of these diseases in humans. This new model will be used to study pharmacological chaperones, small molecules that can bind and stabilize mutated enzyme. This allows the misfolded enzyme to reach the lysosome and degrade stored material correctly. The two chaperones that will be studied have been previously shown to increase both HexA and HexB enzyme in healthy mice. The project will look for increased enzyme activity and reduced ganglioside storage in the brain. The mouse model will also be made available for other late onset research.

About the Katie & Allie Buryk Research Fund

After being diagnosed with Late Onset Tay-Sachs disease, Katie Buryk and her family established a fund to raise money for research for a cure. Read more: Katie & Allie Buryk Research Fund